EP1588766A1 - System und Verfahren zur Kontrolle der Integrität und der Operation von Pipettiervorrichtungen zur Manipulation flüssiger Proben - Google Patents

System und Verfahren zur Kontrolle der Integrität und der Operation von Pipettiervorrichtungen zur Manipulation flüssiger Proben Download PDF

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Publication number
EP1588766A1
EP1588766A1 EP05105471A EP05105471A EP1588766A1 EP 1588766 A1 EP1588766 A1 EP 1588766A1 EP 05105471 A EP05105471 A EP 05105471A EP 05105471 A EP05105471 A EP 05105471A EP 1588766 A1 EP1588766 A1 EP 1588766A1
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EP
European Patent Office
Prior art keywords
pipette tip
air pressure
defective
nozzle
fluid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05105471A
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English (en)
French (fr)
Inventor
Timothy R. Hansen
Gene Alan Benton
Matthew J. Armstrong
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Becton Dickinson and Co
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Becton Dickinson and Co
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Filing date
Publication date
Application filed by Becton Dickinson and Co filed Critical Becton Dickinson and Co
Publication of EP1588766A1 publication Critical patent/EP1588766A1/de
Withdrawn legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0275—Interchangeable or disposable dispensing tips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0275—Interchangeable or disposable dispensing tips
    • B01L3/0279—Interchangeable or disposable dispensing tips co-operating with positive ejection means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1011—Control of the position or alignment of the transfer device
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/103—General features of the devices using disposable tips

Definitions

  • the present invention relates to a system and method for verifying the integrity of the condition and operation of a pipetter device for manipulating fluid samples in test tubes. More particularly, the present invention relates to a system and method for an automated pipetter device that makes use of pressure transducers to detect the presence and integrity of filtered pipette tips on the nozzle of the device, and to sense liquid levels in test tubes from which the pipetter device draws fluid samples.
  • nucleic acid sequencing direct detection of particular nucleic acids sequences by nucleic acid hybridization, and nucleic acid sequence amplification techniques
  • This process generally includes the steps of collecting a sample containing the cells of interest in a sample tube. The sample is then treated with heat or heat plus reagent, which causes the cells to rupture and release the nucleic acids (DNA or RNA) into the solution in the tube.
  • the sample tube is placed in a centrifuge and spun down to separate the cells from other sample components. The resulting pellet is then re-suspended with an appropriate buffer and lysed as described above.
  • the lysed solution containing free nucleic acids is removed from the sample tube by a pipette or any suitable instrument.
  • the solution is then transferred to other tubes or microtiter wells containing reagents necessary for the desired downstream application.
  • One such application, the amplification and detection of specific nucleic acid sequences requires the addition of priming sequences, fluorescein probes, enzymes, and other reagents.
  • the nucleic acids are then detected in an apparatus such as the BDProbeTec® ET system, manufactured by Becton, Dickinson and Company and described in U.S. Patent No. 6,043,880 to Andrews et al., the entire contents of which is incorporated herein by reference.
  • Drawbacks of this approach include the higher cost of conductive pipette tips, and that the method only works effectively with ionic fluids. In other words, if the fluid is non-conductive, it will not provide a suitable electrical path to complete the circuit between the conductors in the pipette tip.
  • a system and method for the measurement of the level of fluid in a pipette tube has been described in U.S. Patent No. 4,780,833, issued to Atake, the contents of which are herein incorporated by reference.
  • Atake's system and method involves applying suction to the liquid to be measured, maintaining liquid in a micro-pipette tube or tubes, and providing the tubes with a storage portion having a large inner diameter and a slender tubular portion with a smaller diameter.
  • a pressure gauge is included for measuring potential head in the tube or tubes. Knowing the measured hydraulic head in the pipette tube and the specific gravity of the liquid, the amount of fluid contained in the pipette tube can be ascertained.
  • Devices used in molecular biology methodologies can incorporate the pipette device mentioned above, with robotics, to provide precisely controlled movements to safely and carefully move sample biological fluids from one container to another.
  • these robotic devices are capable of coupling to one or more of the aforementioned pipette tips, and employ an air pump or other suitable pressurization device to draw the sample biological fluid into the pipette tips.
  • these robotic systems presently have no suitable mechanism to determine whether any of the pipette tips are defective or have been properly acquired by the robot.
  • a further object of the invention is substantially achieved by providing a method for discarding a non-defective pipette tip, comprising controlling an ejection assembly to engage said pipette tip from said nozzle, creating an air flow in said nozzle, determining whether said air flow causes a change in pressure in said nozzle and if said determining determines that substantially no pressure change has occurred ascertaining that the non-defective pipette tip has not been discarded.
  • An additional system for discarding a non-defective pipette tip, comprising an air pump with a nozzle, a pressure transducer, adapted to measure a change in air pressure in the nozzle as the pipette tip is acquired by the nozzle, and an ejection assembly adapted to eject a non-defective pipette tip.
  • Another method according to the present invention is provided for detecting a level of liquid in a container using a pipette tip, comprising moving the pipette tip toward the liquid in the container without aspirating through said pipette tip while detecting for a change in air pressure in said pipette tip, and ascertaining that the pipette tip has entered the fluid holding container when said change in air pressure is detected.
  • a system for detecting a level of fluid in a container using a pipette tip comprising an air pump in communication with a nozzle, and a pressure transducer, adapted to measure a change in air pressure in the nozzle as the pipette tip is inserted onto the fluid holding container.
  • FIGS 1 and 2 illustrate a typical implementation of a robotic pipetting system pipetter device and pipette tip, for manipulating fluid samples which employs a system and method according to an embodiment of the invention.
  • Pipetter device 200 attached to the end of a robotic arm 102, can acquire disposable pipette tips 202 from a holder onto the pipetter device nozzle 204.
  • the disposable pipette tips 202 are used to transfer biological (fluid) samples 218 from one container 216 in a diagnostic process to another. Each fluid sample 218 transfer requires a new pipette tip 202 to prevent cross contamination between fluid samples 218. Additionally, each pipette tip 202 contains a filter 206 that prevents the fluid sample 218 from contaminating the nozzle 204 of the pipetter device 200. As shown in Figure 2, the pipetter device 200 employs a pressurization apparatus such as air pump 210, with piston 210A.
  • air pump 210 The interior portion of air pump 210 is an air pump chamber 214 and is in communication with pressure transducer 208, which measures the air pressure within the cavity formed within air pump 210 nozzle 204 of pipetter device 200 and pipette tip 202. Shown also in Figure 2 are originating position 212 and overdrive position 224, which conveys the extent of travel of piston 210 within air pump 210. These features will be discussed in detail below.
  • Figures 3-6 illustrate various views of an industrial application of the pipetter device 200 and pipette tip 202 shown in Figures 1 and 2.
  • Figure 3 illustrates a frontal view.
  • motor 302 is shown connected to lead screw 304.
  • Lead screw 304 is, in turn, also connected to piston drive bar 306.
  • Piston drive bar 306 is connected to actuating bars 310A and 310B, and both actuating bars 310A, 310B are connected to ejection bar 312.
  • Springs 310A (left side) and 310B (right side) act upon body part 314 to resist downward motion of piston drive bar 306, and actuating bars 310A, 310B and ejection bar 312.
  • springs 308A, 308B are chiefly intended to assist in returning the aforementioned components to their resting position.
  • the combination of motor 302, lead screw 304, piston drive bar 306, springs 308A, 308B, actuating bars 310A, B and ejection bar 312, comprise the tip ejection assembly.
  • the tip ejection assembly is designed to facilitate easy insertion of pipette tips 202 into nozzles 204, yet provide a reliable means and manner for proper ejection of used and/or defective pipette tips 202.
  • Ejection bar 312 performs the physical ejection of pipette tips 202.
  • Ejection bar 312 has a plurality of holes; each hole allowing nozzle 204 to pass through it, so that it might be received into a pipette tip 202.
  • pipette tip 202 cannot pass through ejection bar 312, because at the very bottom of pipette tip 202, there is a flange 203 having a dimension larger than the body of pipette tip 202 and larger than the diameter of the holes in ejection bar 312.
  • pipette tip adapters 316 with upper adapter flange 318A and lower adapter flange 318B.
  • Upper adapter flange 318A and lower adapter flange 318B mate with pipette tip 202, providing a two-point seal that inn turn provides an air-tight interface between pipetter device 200 and pipette tip 202.
  • motor 302 turns lead screw 304, which in turn forces piston drive bar 306 down.
  • piston drive bar 306 moves down, it forces actuating bars 310A, 310B down.
  • This movement causes ejection bar 312 to move down, until ejection bar 312 encounter flanges 203 of pipette tips 202.
  • Flange 203 and ejection bar 312 come in contact and as ejection bar 312 continues its downward movement, it ejects pipette tips 202 from its mated connection with nozzle 204.
  • motor 302 reverses and all the components of the tip ejection assembly move in the opposite direction.
  • Figures 4-6 show different views of pipetter device 200 and pipette tip 202.
  • Figure 4 is a right side view;
  • Figure 5 is a bottom-perspective view;
  • Figure 6 is a front-perspective view.
  • Figure 7 illustrates a conceptual block diagram of a controller board assembly used with the system shown in Figure 1. It is well known in the art that a robotic arm 102 may be controlled by a controller board 726 that is part of controller assembly 700. Controller board 726 may contain processor 716 and memory 718 that stores executable software (system software) 722 that controls operation of robotic arm 102, and pipetter device 200.
  • system software system software
  • controller assembly 700 will be designed to be able to control numerous robotic arms 102.
  • the number of robotic arms 102 able to be controlled by a single controller board is dependent upon several factors, including, but not limited to, the processing capability of processor 716 on the controller board, data acquisition rates, amount of memory, difficulty of tasks the robotic arms must perform, and how much data must be acquired about environmental conditions or the manufacturing process itself.
  • a typical controller assembly includes controller board 726, data and control cables 704A-C and 706 that can be coupled to display 724, motor 702 (that can control movement of piston 210A), pressure transducer 208 and robotic arm 102.
  • Data and control cables 704A-C might also be one continuous cable in some particular applications.
  • controller board 726 includes memory 718, which contains system software 722, and can be connected by internal bus 724 to processor 716.
  • Processor 716 can be connected to network card 720, by a second internal bus 726, which can transfer collected data to and from network computer 730.
  • Processor 716 can communicate with analog-to-digital converter (ADC) 714 and input/output devices (I/O) 708A by internal bus 724.
  • ADC analog-to-digital converter
  • I/O input/output devices
  • I/O 708B is a different type of interface. Because it receives analog signals, these often require special cabling and coupling techniques to prevent the coupling of noise onto the signal. I/O 708B are often separated from purely digital signals for these reasons.
  • the received analog signal from I/O 708B is first processed by AMP/filter 714, which may contain an amplifier, filter, or even a level shifter, depending on the nature of the analog signal and ADC 712.
  • Controller assembly 700 used in conjunction with an embodiment of the invention, is shown having a single ADC 712 and amplifier circuit 714.
  • the amplifier 714 might also include a filter, which might be necessary depending on the nature of the analog signal received by controller board 726.
  • Controller board 726 communicates with robotic arm 102 via control/data bus 704B.
  • Control bus 704A transmits control data from processor 716 to robotic arm 102, and receives data from robotic arm 102, which is reported to processor 716. In this manner, motion control data is given to robotic arm 102, and motion data that reports the movement of robotic arm 102 is fed back to processor 716, providing a means for checking the movement and positioning of robotic arm 102.
  • Such data can include relative and absolute position in three axes (x, y and z), and relative and absolute velocity, acceleration and even angular velocities and acceleration measurements in the three axes.
  • Controller assembly 700 communicates in a similar fashion with motor 302.
  • Control/data bus 704A transmits control data to motor 302, which controls the movement of piston 210A of air pump 210.
  • Pressure transducer 208 outputs an analog pressure transducer (APT) signal 732, transmitted on analog signal line 706, which is connected to I/O 708B on controller board 726.
  • APT analog pressure transducer
  • APT signal 732 is input to AMP/filter 714, which then outputs conditioned APT signal 734 to ADC 712.
  • ADC 712 converts conditioned APT signal 734 to a digital word, which can be processed by processor 716.
  • processor 716 ascertains the air pressure in pipetter device 200, and the methods of the invention including determining the volume of liquid in pipette device 200, determining whether or not pipette tip 202 has entered fluid sample 218, and determining whether or not a defective pipette tip 202 has been acquired by the robotic arm, and if not defective, when it has been discarded.
  • Figure 8 illustrates a graph depicting an example of air pressure versus time during pipette tip acquisition, for a non-defective pipette tip.
  • robotic arm 102 moves pipetter device 200 to a holder that contains one or more pipette tips 202 (time T 0 in Figure 8).
  • Robotic arm 102 then positions nozzle 204 of the pipetter device 200 over a pipette tip 202 and pushes the nozzle 204 into pipette tip receptacle 202A (time T 1 in Figure 8).
  • any increase in air pressure recorded by pressure transducer 208 is shown as a positive value (above the x axis). This is the situation when air enters pipette tip 202. If air is released, or a vacuum created, air pressure is shown decreasing or becoming a negative value.
  • Pressure transducer 208 mounted between the nozzle 204 and air pump 210 detects this momentary increase in air pressure and allows system software 722 to identify that a non defective pipette tip 202 has been acquired, and that filter 206 is in pipette tip 202.
  • the air pressure measured by transducer 208 has reached a maximum, and begins to decay from time T 2 to T 3 .
  • filter 206 allows the air pressure to decrease to 0. This occurs because filter 206 is porous.
  • the periods T 1 to T 2 , and T 2 to T 3 are dependent upon the type of filter 206 (i.e. what materials and manufacturing method used), and how fast nozzle 204 is inserted into pipette tip 202 (for the T 1 to T 2 period). In some applications, it is necessary for the air pressure to return to 0.
  • system software 722 will instruct robotic arm 102 to reject pipette tip 202 and acquire a new pipette 202 tip from the next location. Ejection of a defective pipette tip 202 is discussed in detail with respect to Figure 9.
  • Figure 9 illustrates a graph depicting an example of air pressure versus time during pipette tip acquisition, and its subsequent ejection, for a defective pipette tip.
  • robotic arm 102 is moving to acquire pipette tip 202.
  • pipette tip 202 is acquired, and the nozzle is inserted in the period of time defined between T 1 and T 2 .
  • system software 722 notes that no change in air pressure has occurred. Therefore, from time T 2 to T 3 , robotic arm 102 moves pipette device 200 to a position in which defective pipette tip 202 can be discarded.
  • robotic arm 102 moves from pipette tip 202 acquisition location, to an area where used or defective pipette tips 202 can be discarded, usually a waste container. This occurs from time T 2 to time T 3 .
  • Pipette tips 202 are ejected from pipetter device 200 by over-driving the air pump 210 piston 210A to overdrive position 224 in air pump chamber 214, which engages the tip ejector assembly, and ejects defective pipette tips 202 into a waste container. The process by which this occurs was described above in detail with respect to Figures 3-7. Because pipette tip 202 is defective (i.e. no filter 206). There will be no change in air pressure, even though piston 210A has moved to overdrive position 224. All the air simply escapes through the unrestricted opening 220 of pipette tip 202.
  • piston 210A then moves to its originating position, which occurs at time T 4 , the air pressure will not change. This is because there is no restriction to the flow of air within pipetter device 200.
  • robotic arm 102 can move pipetter device 200 to its starting position, or to a position to acquire a new pipette tip 202. While robotic arm is moving pipetter device 200, piston 210A is recovering from its overdrive operation.
  • Figure 10 illustrates a graph depicting an example of air pressure versus time during ejection of a non-defective pipette tip.
  • a non-defective tip has already been acquired, and may have been used, but that in any case, it is desirable to eject it, and to acquire a new pipette tip 202 for a new use.
  • motor 302 is beginning to move piston 210A to overdrive position 224. This action also caused lead screw 304 to engage the tip ejection assembly, which ultimately causes ejection bar 312 to force the non-defective pipette tip(s) 202 off nozzle(s) 204. Because these are non-defective pipette tips 202, filter 206 will restrict air being forced out of air pump chamber 214, and air pressure will rise. Pressure transducer 208 measures this air pressure rise and this information is communicated to controller board 726, and ultimately processor 716.
  • the tip ejection assembly has moved to a position where ejection bar 312 should force pipette tip 202 away from nozzle 204.
  • the measured air pressure should, for a proper ejection, drop to a reading of, or about, zero.
  • the ejection period could be sudden, but it might also be gradual; however, in a proper ejection of a non-defective pipette tip 202 the decrease in air pressure from T 2 to T 3 will be very quick. Therefore, at some short time later T 4 , a subsequent air pressure reading should indicate at, or about, zero, indicating no significant air pressure measured by pressure transducer 208.
  • Processor 716 recognizes that the air pressure should have returned to zero by the time T 4 , or even T 5 , but it has not. Therefore, it will attempt the tip ejection process again. As in the case of a non-defective pipette tip 202 acquisition, discussed in reference to Figure 8, air pressure will eventually begin to reduce because of the porous nature of filter 206. This is shown in the drop of pressure at T 5 .
  • piston 210A From time T 5 to T 6 piston 210A returns to its originating position 212, and causes the air pressure to return to, or about, zero. At some time later T 7 , the ejection process will begin again. Measured air pressure will rise, and at time T 8 the ejection assembly will again have moved to the position where ejection should have occurred. Thus, by measuring the air pressure through pressure transducer 208, processor 716 can quickly determine whether non-defective pipetting tip 202 was properly ejected, and if not, re-active the tip ejection procedure.
  • Figure 11 illustrates a graph depicting an example of air pressure versus time during insertion of a pipette tip into a fluid sample.
  • fluids 218 in a container 216 is determined by measurement of the signal generated by pressure transducer 208. Even a short insertion, e.g. several millimeters, of pipette tip 202 into fluid sample 218, will cause a pressure change, readily ascertainable by pressure transducer 208 and system software 722.
  • robotic arm 102 moves pipetter device 200 into position during the period of time from T 0 to T 1 .
  • T 1 to T 2 pipette tip 202 is moved into fluid sample 218.
  • fluid sample 218 compresses the air inside of pipette tip 202. This compression registers as pressure reading P 1 .
  • system software 722 commands robotic arm 102 to stop moving pipette tip 202 further into container 216. This occurs at time T 2 .
  • Pipetter device 200 then aspirates fluid sample 218 into opening 220 of pipette tip 202, which is submerged in fluid sample 218. This occurs from time T 2 to T 3 , and the pressure changes from P 1 to P 2 . P 2 is negative because air pump 210 is creating a vacuum to draw fluid sample 218 into pipette tip 202. As fluid is drawn into pipette tip 202, robotic arm 102 moves pipette tip 202 downward into container 216 at a speed based on the rate of aspiration and the diameter of the container 216.
  • the volume of fluid aspirated into the pipette tip can be verified using pressure transducer 208.
  • pressure transducer 208 For example, U.S. patent No. 4,780,833, the contents of which are incorporated herein by reference, describes a system and method for determining the volume of a liquid sample drawn into a similar pipetter device 200, by measuring the head pressure above the fluid column with knowledge of the fluid's specific gravity.
  • P 3 is the air pressure that corresponds directly to the volume of liquid in pipette tip 202.
  • P 2 is the air pressure equal to the volume of aspirated fluid plus the friction force of the aspirated fluid sample 218A to pipette tip 202 (inner wall surface) interface, due to surface tension.
  • the measured air pressure is equivalent to the weight of aspirated fluid sample 218A, and through use of its specific gravity (which is known, a priori), the fluid's volume is likewise known.
  • robotic arm 102 From time T 4 to T 5 , robotic arm 102, at the command of system software 322, moves pipette device 200 to another location where another container, 216A, might be located to dispense the aspirated fluid into.
  • piston 210A begins pumping the aspirated fluid out, and at time T 6 the desired amount of fluid has been expelled.
  • the resultant pressure, P 4 or P 4 might still be negative (i.e., in the case that only a small amount of aspirated fluid was pumped out, and there is still a negative pressure retaining the fluid) or positive (i.e., in the case that all or nearly all of the fluid pumped out, requiring greater "pumping" force).
  • FIG. 12 illustrates a flow diagram of a first method according to an embodiment of the invention.
  • the flow diagram illustrated in Figure 12 shows the steps in a method for detecting defective pipette tips, as discussed above.
  • the method begins with step 1202, in which pressure transducer 208 measures a first air pressure, which is recorded by processor 716.
  • step 1204 robotic arm 102 moves pipetter device 200 such that nozzle 204 may be inserted over pipette tip receptacle 202A of pipette tip 202.
  • a second air pressure is measured and recorded, soon after the pipette tip 202 has been inserted over nozzle 204.
  • Processor 716 compares the first air pressure to the second air pressure: If the second air pressure is greater than the first air pressure, then a non-defective pipette tip 202 has been acquired by robotic arm 102, and it may be used for acquiring fluids (yes path 1210 from decision box 1208).
  • processor 716 determines that a defective pipette tip 202 has been acquired, and can discard it, using the ejection process discussed in reference with Figure 9 (no path 1212 from decision box 1208).
  • FIG. 13 illustrates a flow diagram of a second method according to another embodiment of the invention.
  • the flow diagram illustrated in Figure 13 shows the steps in a method for determining whether a non-defective pipette tip has been ejected, as discussed above.
  • the method according to Figure 13 begins with step 1302.
  • step 1302 air pressure is measured continuously by pressure transducer 208, and recorded by processor 716.
  • step 1304 processor 716 decides to eject the non-defective pipette tip 202, and causes robotic arm to engage the tip ejection assembly.
  • Engaging the tip ejection assembly means that motor 302 begins to overdrive air pump 210, and turn lead screw 304, etc., as described with reference to Figures 3-6.
  • processor 716 again monitors the measured air pressure:
  • processor 716 compares the air pressure just before piston bar 210 reached overdrive position 224, and the air pressure just after piston bar reached overdrive position 224, to determine whether a substantial and sudden decrease in air pressure has occurred. This decrease in air pressure would be caused by air being suddenly released when pipette tip 202 was forcibly ejected from nozzle 204, and the pressurized air in air pump chamber 214 and pipette tip receptacle 202A was released into the atmosphere. If there was a sudden and substantial decrease in the measured air pressures, then pipette tip 202 was properly ejected (yes path 1310 from decision box 1308).
  • the processor 716 determines that pipette tip 202 was not properly ejected (no path 1712 from decision box 1708). It will cause piston bar 210 to return to an intermediate position (i.e., between its originating position and overdrive position) and begin the process of ejecting pipette tip 202 again (i.e., it returns to step 1304). It may do this several times before pipette tip 202 is properly ejected.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
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  • Analytical Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
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  • Measurement Of Levels Of Liquids Or Fluent Solid Materials (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
EP05105471A 2002-02-13 2003-02-12 System und Verfahren zur Kontrolle der Integrität und der Operation von Pipettiervorrichtungen zur Manipulation flüssiger Proben Withdrawn EP1588766A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US10/073,207 US20040149015A1 (en) 2002-02-13 2002-02-13 System and method for verifying the integrity of the condition and operation of a pipetter device for manipulating fluid samples
US73207 2002-02-13
EP03003077A EP1338339B1 (de) 2002-02-13 2003-02-12 System und Verfahren zur Kontrolle der Integrität des Zustands und der Operation von Pipettiervorrichtungen zur Manipulation flüssiger Proben

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EP03003077A Expired - Lifetime EP1338339B1 (de) 2002-02-13 2003-02-12 System und Verfahren zur Kontrolle der Integrität des Zustands und der Operation von Pipettiervorrichtungen zur Manipulation flüssiger Proben

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US (1) US20040149015A1 (de)
EP (2) EP1588766A1 (de)
JP (1) JP2004037446A (de)
AT (1) ATE340646T1 (de)
CA (1) CA2418628A1 (de)
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JP4599397B2 (ja) * 2005-03-10 2010-12-15 富士通株式会社 ポンプユニット、シリンジユニット、粒子送出方法、および細胞送出方法
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JP5669340B2 (ja) 2008-01-23 2015-02-12 シスメックス株式会社 試料分析装置及び試料分析装置用プログラム
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JP2015187592A (ja) * 2013-07-02 2015-10-29 富士フイルム株式会社 血液試料分注用アダプタ並びにそれを備えた分注キット及び針キット
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US10379131B2 (en) * 2015-11-18 2019-08-13 Elbit Systems Of America/Kmc Systems, Inc. Systems and methods for detecting a liquid level
CN108713146B (zh) * 2016-03-22 2021-11-30 富士胶片株式会社 溶液排出装置及溶液的排出控制方法
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CN114849807A (zh) * 2022-03-02 2022-08-05 深圳市爱康生物科技股份有限公司 一种多通道脱针装置及脱针方法
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DE60308571D1 (de) 2006-11-09
DE60308571T2 (de) 2007-06-28
ATE340646T1 (de) 2006-10-15
CA2418628A1 (en) 2003-08-13
EP1338339A1 (de) 2003-08-27
EP1338339B1 (de) 2006-09-27
MXPA03001262A (es) 2005-08-26
US20040149015A1 (en) 2004-08-05

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